Central Vein Sign as a Biomarker for New Multiple Sclerosis Lesions

In a longitudinal study, researchers aimed to identify the presence of CVS in new white matter lesions in patients with MS and investigate demographic and clinical risk factors associated with CVS development.

The majority of newly developing T2 lesions or new enhancing lesions in adults with multiple sclerosis (MS) showed positive central vein sign (CVS) on imaging, according to findings published recently in Neurology Neuroimmunology & Neuroinflammation. Nearly half of these adults developed new lesions with positive central vein sign only.

CVS is a central linear hypointensity frequently observed in MS lesions that can be visualized on T2-weighted magnetic resonance imaging. It corresponds to the small vein or venule found in MS lesions. CVS is considered an imaging sensitive and specific biomarker for MS and can distinguish MS from other etiologies. However, it has not been studied in depth in MS lesions that are newly developing.

The objective of the current study was to analyze over time the presence of CVS in new lesions among patients with MS while investigating demographic and clinical risk factors associated with CVS development.

The researchers conducted a retrospective longitudinal cohort study (ClinicalTrials.gov Identifier: NCT00001248) of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) from the NIH MS Natural History Study, of whom, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1–Q3: 0.7–6.3) of follow-up.

In 62 (65%) of the participants, lesions suitable for study evaluation were found. Of the 233 such lesions, 159 (68%) were CVS+ (a “positive” CVS means seeing the vessel in two or more perpendicular planes to assure it is “central”), with 30 (48%) individuals having only CVS+, 12 (19%) only CVS−, and 20 (32%) both CVS+ and CVS− lesions. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3–0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1–1.9) were associated with increased likelihood of new CVS+ lesion development.

Over a median duration of 3 years, in adults with MS, “most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (of the participants with study lesions) (48%) developed new CVS+ lesions only…Patients who developed new lesions were more likely to be younger and have a relapsing-remitting MS diagnosis with shorter disease duration.”

Study limitations included that few participants had progressive MS, and, few participants with newly developing lesions had comorbid vascular disease.

Previous research has established the increased prevalence of vascular risk factors in patients with MS. Researchers in this study linked baseline CVS+ percentage with the likelihood of new CVS+ development over time.

They concluded, “These results underscore the need for prospective studies examining the influence of disease-modifying therapy changes on the likelihood of new lesion development stratified by CVS characteristics and the impact of vascular risk factors.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Al-Louzi O, Letchuman V, Manukyan S, et al. Central vein sign profile of newly developing lesions in multiple sclerosis: A 3-year longitudinal study. Neurol Neuroimmunol Neuroinflamm. Published online, January 13, 2022. doi:10.1212/NXI.0000000000001120